Assessment of liver viscoelasticity by using shear waves induced by ultrasound radiation force.

PURPOSE: To investigate the value of viscosity measured with ultrasonographic (US) elastography in liver fibrosis staging and to determine whether the use of a viscoelastic model to estimate liver elasticity can improve its accuracy in fibrosis staging. MATERIALS AND METHODS: The study, which was performed from February 2010 to March 2011, was compliant with HIPAA and approved by the institutional review board. Written informed consent was obtained from each subject. Ten healthy volunteers (eight women and two men aged 27-55 years) and 35 patients with liver disease (17 women and 18 men aged 19-74 years) were studied by using US elasticity measurements of the liver (within 6 months of liver biopsy). US data were analyzed with the shear wave dispersion ultrasound vibrometry (SDUV) method, in which elasticity and viscosity are measured by evaluating dispersion of shear wave propagation speed, as well as with the time-to-peak (TTP) method, where tissue viscosity was neglected and only elasticity was estimated from the effective shear wave speed. The hepatic fibrosis stage was assessed histologically by using the METAVIR scoring system. The correlation of elasticity and viscosity was assessed with the Pearson correlation coefficient. The performances of SDUV and TTP were evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: The authors found significant correlations between elasticity and viscosity measured with SDUV (r = 0.80) and elasticity measured with SDUV and TTP (r = 0.94). The area under the ROC curve for differentiating between grade F0-F1 fibrosis and grade F2-F4 fibrosis was 0.98 for elasticity measured with SDUV, 0.86 for viscosity measured with SDUV, and 0.95 for elasticity measured with TTP. CONCLUSION: The results suggest that elasticity and viscosity measured between 95 Hz and 380 Hz by using SDUV are correlated and that elasticity measurements from SDUV and TTP showed substantially similar performance in liver fibrosis staging, although elasticity calculated from SDUV provided a better area under the ROC curve.

Handheld array-based photoacoustic probe for guiding needle biopsy of sentinel lymph nodes.

By modifying a clinical ultrasound array system, we develop a novel handheld photoacoustic probe for image-guided needle biopsy. The integration of optical fiber bundles for pulsed laser light delivery enables photoacoustic image-guided insertion of a needle into rat axillary lymph nodes with accumulated indocyanine green (ICG). Strong photoacoustic contrast of the needle is achieved. After subcutaneous injection of the dye in the left forepaw, sentinel lymph nodes are easily detected, in vivo and in real time, beneath 2-cm-thick chicken breast overlaying the axillary region. ICG uptake in axillary lymph nodes is confirmed with fluorescence imaging both in vivo and ex vivo. These results demonstrate the clinical potential of this handheld photoacoustic system for facile identification and needle biopsy of sentinel lymph nodes for cancer staging and metastasis detection in humans.

Sentinel lymph nodes in the rat: noninvasive photoacoustic and US imaging with a clinical US system.

PURPOSE: To evaluate in vivo sentinel lymph node (SLN) mapping by using photoacoustic and ultrasonographic (US) imaging with a modified clinical US imaging system. MATERIALS AND METHODS: Animal protocols were approved by the Animal Studies Committee. Methylene blue dye accumulation in axillary lymph nodes of seven healthy Sprague-Dawley rats was imaged by using a photoacoustic imaging system adapted from a clinical US imaging system. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken or turkey breast on top of the rat skin surface. Three-dimensional photoacoustic images were acquired by mechanically scanning the US transducer and light delivery fiber bundle along the elevational direction. RESULTS: Photoacoustic images of rat SLNs clearly help visualization of methylene blue accumulation, whereas coregistered photoacoustic/US images depict lymph node positions relative to surrounding anatomy. Twenty minutes following methylene blue injection, photoacoustic signals from SLN regions increased nearly 33-fold from baseline signals in preinjection images, and mean contrast between SLNs and background tissue was 76.0 +/- 23.7 (standard deviation). Methylene blue accumulation in SLNs was confirmed photoacoustically by using the optical absorption spectrum of the dye. Three-dimensional photoacoustic images demonstrate dynamic accumulation of methylene blue in SLNs after traveling through lymph vessels. CONCLUSION: In vivo photoacoustic and US mapping of SLNs was successfully demonstrated with a modified clinical US scanner. These results raise confidence that photoacoustic and US imaging can be used clinically for accurate, noninvasive imaging of SLNs for axillary lymph node staging in breast cancer patients.

Deeply penetrating in vivo photoacoustic imaging using a clinical ultrasound array system.

Using a hand-held photoacoustic probe integrated with a clinical ultrasound array system, we successfully imaged objects deeply positioned in biological tissues. The optical contrasts were enhanced by methylene blue with a concentration of ~30 mM. The penetration depth reached ~5.2 cm in chicken breast tissue by using 650-nm wavelength, which is ~4.7 times the 1/e optical penetration depth. This imaging depth was achieved using a laser fluence on the tissue surface of only 3 mJ/cm(2), which is 1/7 of the American National Standards Institute (ANSI) safety limit (20 mJ/cm(2)). The noise equivalent sensitivity at this depth was ~11 mM. Further, after intradermal injection of methylene blue in a rat, a sentinel lymph node was easily detected in vivo, beneath a 2-cm thick layer of chicken breast. Also, blood located 3.5 cm deep in the rat was clearly imaged with intrinsic contrast. We have photoacoustically guided insertion of a needle into a rat sentinel lymph node with accumulated methylene blue. These results highlight the clinical potential of photoacoustic image-guided identification and needle biopsy of sentinel lymph nodes for axillary staging in breast cancer patients.